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Cardiology Group Issues Guidelines That Include Aldosterone Blockers

NEW YORK, Aug. 16 /PRNewswire/ -- Patients who have had a recent heart attack with ST-elevation (ST-Elevation Myocardial Infarction, or STEMI), complicated by heart failure should be treated with aldosterone blockers according to new guidelines issued recently by the American College of Cardiology (ACC) and the American Heart Association (AHA).(1) The new ACC/AHA STEMI guidelines regarding aldosterone blockade are based in part on the landmark EPHESUS(TM) (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) clinical trial, the results of which were published in The New England Journal of Medicine on April 3, 2003. The EPHESUS(TM) study demonstrated significant survival benefits in post-MI patients with evidence of heart failure.

"The new STEMI guidelines have important implications for improving the care of patients post-myocardial infarction," said Bertram Pitt, MD, Professor of Internal Medicine, University of Michigan Health System. "They emphasize the importance of treating patients with evidence of heart failure following an acute myocardial infarction with an aldosterone blocking agent. The results of EPHESUS clearly show that we can improve mortality as well as the incidence of cardiovascular hospitalization in these patients by adding the aldosterone blocker, eplerenone, to our current treatment strategies."

STEMI is a heart attack causing damage to the heart muscle, recognized on an electrocardiogram by elevation of the ST segment. This injury often leads to weakening of the heart muscle and may result in heart failure. Like all heart attacks, STEMI is associated with an increased risk of cardiac death.(2) An estimated 500,000 STEMI events occur each year in the US.(1) Furthermore, more than 30% of all acute myocardial infarctions (AMIs) are complicated by heart failure.(3)

The new ACA/AHA STEMI guidelines recognize the body of evidence supporting the role of aldosterone blockade in reducing cardiovascular events. Aldosterone blockers received the highest "Class I, Level of Evidence A" endorsement by the Guidelines Committee.(1) Class I means that a treatment should be administered, and Level A means that there is ample clinical evidence to support the administration of the treatment.(1)

The guidelines, published in the current issues of Circulation and the Journal of the American College of Cardiology, recommend that aldosterone blockade therapy be initiated in the hospital and also prescribed for long- term use. Specifically, the guidelines recommend that "long-term aldosterone blockade should be prescribed for post-STEMI patients without significant renal dysfunction (creatinine should be less than or equal to 2.5 mg/dL in men and less than or equal to 2.0 mg/dL in women) or hyperkalemia (potassium should be less than or equal to 5.0 mEq/L) who are already receiving therapeutic doses of an ACE inhibitor, have a LVEF less than or equal to 0.40, and have either symptomatic heart failure or diabetes."(1)

The new guidelines for the use of aldosterone blockade reference the EPHESUS(TM) clinical trial, which included over 6,600 patients from 37 countries.(1) In EPHESUS(TM), patients who had an acute heart attack complicated by heart failure were treated with either the aldosterone blocker eplerenone (INSPRA(R)) along with standard therapy or with placebo and standard therapy. Those patients treated with INSPRA had a significant reduction in overall mortality and hospitalizations.(5)

Clinical Evidence from EPHESUS(TM)
In EPHESUS(TM), treatment with INSPRA in addition to available standard therapies reduced the risk of death by 15 percent among post-MI patients who had low ejection fraction (less than or equal to 40%) and evidence of heart failure compared to treatment with placebo and standard therapy. Standard therapy could include ACE inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, diuretics, statins, aspirin, and cardiac reperfusion therapy. The use of INSPRA with standard therapy also further reduced cardiovascular mortality/cardiovascular hospitalization by 13 percent and sudden cardiac death by 21 percent. Patients were initiated on therapy within 3 to 14 days of the AMI event (mean 7 days) and were followed up for a mean of 16 months.(5)

"The results of the EPHESUS(TM) trial clearly demonstrate that treatment with INSPRA (eplerenone) in patients post-MI who have evidence of heart failure can improve outcomes such as prolonging lives and reducing hospitalizations," said Vladyslav Bykoriz, MD., PhD, Medical Director at Pfizer. "The new treatment guidelines, that include aldosterone blockade, provide important information for physicians' treatment of STEMI patients."

About INSPRA
INSPRA(R) (eplerenone) is indicated to improve survival of stable patients with left ventricular systolic dysfunction (ejection fraction less than or equal to 40%) and clinical evidence of congestive heart failure after an acute myocardial infarction. INSPRA is contraindicated in all patients with the following: serum potassium >5.5 mEq/L at initiation; creatinine clearance less than or equal to 30 mL/min; concomitant use with the following potent CYP3A4 inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir, or other drugs described in their labeling as strong inhibitors of CYP3A4.

The principal risk of INSPRA is hyperkalemia. Hyperkalemia can cause serious, sometimes fatal, arrhythmias. Hyperkalemia can be minimized by patient selection, avoidance of certain concomitant treatments, and periodic monitoring until the effect of INSPRA has been established. Patients who develop hyperkalemia (>5.5 mEq/L) may still benefit from INSPRA with proper dose adjustment. Patients with congestive heart failure post-acute MI receiving INSPRA who have renal insufficiency (serum creatinine levels >2 mg/dL [males] or >1.8 mg/dL [females]; creatinine clearance less than or equal to 50 mL/min) or patients with diabetes, including those with proteinuria, should be treated with caution, due to the increased risk of hyperkalemia.

Adverse events that occurred more frequently in patients treated with INSPRA than placebo were hyperkalemia (3.4% vs. 2.0%) and increased creatinine (2.4% vs. 1.5%). Discontinuations due to hyperkalemia or abnormal renal function were less than 1.0% in both groups. Hypokalemia occurred less frequently in patients treated with INSPRA (0.6% vs. 1.6%).

Patients with congestive heart failure post-acute MI receiving INSPRA who have renal insufficiency (serum creatinine levels >2 mg/dL [males] or >1.8 mg/dL [females]; creatinine clearance less than or equal to 50 mL/min) or patients with diabetes, including those with proteinuria, should be treated with caution, due to the increased risk of hyperkalemia.

For full prescribing information, please visit http://www.inspra.com/.

References
(1) Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction - executive summary: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (writing committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction). JACC. Vol 44, No. 3, 2004:August 4,2004:671-719.
(2) Dorland's Illustrated Medical Dictionary. 28th Edition, Philadelphia, PA: WB Saunders & Company; 534.
(3) Hasdai D, Topol EJ, Kilaru R, et al. Frequency, patient characteristics, and outcomes of mild-to-moderate heart failure complicating ST-segment elevation acute myocardial infarction: lessons from 4 international fibrinolytic therapy trials. Am Heart J. 2003;145:73-79.
(4) Brown NJ. Eplerenone cardiovascular protection. Circulation. 2003;107:2512-2518.
(5) Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. NEJM. 2003;348:1309-1321.

Source: Pfizer, Inc.

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